It is generally recognized that high blood cholesterol levels are significant risk factors in cardiovascular disease. Studies have demonstrated that with very few exceptions, populations which consume large quantities of saturated fat and cholesterol have relatively high concentrations of serum cholesterol and a high mortality rate from coronary heart disease. On the other hand, populations which consume large amounts of cereal grains tend to have lower incidences of cardiovascular disease.
Palm oil is commonly classified as a saturated fat and is grouped together with lard, butter fat, hydrogenated vegetable oils, coconut oil and palm kernel oil. Animal and human experiments with palm oil-enriched diets, however, have unexpectedly demonstrated that palm oil feeding does not raise serum cholesterol but in fact it lowers it. An explanation for palm oil's hypocholesterolemic effects despite its fatty acid composition of approximately 50% of the saturated fatty acids and 50% of unsaturated fatty acids was needed.
Studies of cereal grains revealed that barley was particularly effective in lowering lipid levels in animal models. Qureshi et al., Atherosclerosis, 51: 75-87, (1984). The ability of barley extracts to lower lipids in vivo prompted the purification and identification of the chemical constituents responsible for cholesterol suppressive activity. alpha-Tocotrienol was recovered from barley extracts using state-of-the-art methods and was designated as the biologically active component based on subsequent in vitro and in vivo evaluation. Qureshi et al., J. Biol. Chem., 261: 10544-10550, (1986). A U.S. patent was issued to The Wisconsin Alumni Research Foundation specifically claiming the use of alpha-tocotrienol for the lowering of lipids, U.S. Pat. No. 4,603,142, to Qureshi et al. (1986).
With the disclosure of alpha-tocotrienol as the hypolipidemic component of barley, we initiated a chemistry program to study this and related compounds. It was found that an important group of minor constituent of palm oil is its tocotrienols.
Purified tocotrienols are best obtained from palm oil or latex using published procedures. Whittle et al., Biochem. J., 100: 138-145, (1966); Pennock et al., Biochem. and Biophys. Res. Comm., 17: 542-548, (1966). Synthesis of alpha-tocotrienol was performed according to the literature method of Urano, et al., Chem. Pharm. Bull., 31: 4341-4345, (1983). However, this method was not acceptable since it provided a mixture of side chain olefin isomers. Other literature methods for the synthesis of alpha-tocotrienol are very lengthy and were not practical Mayer, et al., Helv. Chim. Acta, 46: 2517-2526, (1963); Scott, et al., Helv. Chim. Acta, 59:290-306 (1976).